Chemical composition and vasodilator activity of different Alpinia zerumbet leave extracts, a potential source of bioactive flavonoids

A polyphenol-rich extract with an expressive vasodilator effect was obtained from fresh leaves of Alpinia zerumbet (AZ), a medicinal plant. The vasodilator effects of AZ obtained from different extraction conditions were studied in perfused mesenteric vascular bed, and total polyphenol content (TPC) was determined for all samples. Chemical composition of AZ was analyzed by UHPLC/ESI-QTOF-MS, and a list of putative compounds was obtained by a molecular network. Briefly, results obtained indicate a 50% hydroethanolic extract from fresh leaves (AZE4) as the best extraction condition, presenting the greatest vasodilator effect (ED 50 = 7.1 µg ± 1.73) and TPC (16.30 mg GAE/g ± 0.44). Flavonoids were detected as main constituents and alpinetin, kaempferol-3-O-glucuronide, (-)- epicatechin and pinocembrin were identified as major compounds. The last effective extraction condition was 50% hydroethanolic extract from dried leaves without heating, which showed the smallest vasodilator response (ED 50 = 29.1 µg ± 4.3) and TPC (6.35 mg GAE/g ± 0.08), reinforcing the use of fresh leaves and heating step to improve extracts performance. The vasodilator effect and the main flavonoid composition of AZE4 provide experimental support for the indication of this extract as a potential source of bioactive flavonoids for the treatment of cardiovascular diseases.

Synthesis and vasodilator activity of some pyridazin-3(2H)-one based compounds

Aim: Hypertension is a major health problem worldwide resulting in high death rates due to its consequences and complications. Therefore, searching for new vasorelaxants is a must to find new vasodilators efficient for the treatment of different cardiovascular diseases. Methodology: Different 6-phenyl-3-pyridazinone based derivatives were synthesized and screened for their vasorelaxant activity according to the reported method using hydralazine as a standard. Results: The tested compounds revealed potent to mild activity with EC50 values 0.339–114.300 μM compared with hydralazine EC50 = 18.210 μM. Conclusion: The most active compounds were the acid 5, its ester analog 4 and 4-methoxyphenylhydrazide derivative 10c (EC50 = 0.339, 1.225 and 1.204 μM, respectively). Therefore, 6-phenylpyridazin-3(2 H)-one can be a hit for structural optimization to obtain promising vasorelaxants.

Aqueous Extract of Matricaria pubescens Exhibits Antihypertensive Activity in L-NAME-induced Hypertensive Rats through its Vasorelaxant Effect

Background: Matricaria pubescens is a medicinal plant from North Africa. This plant is widely used in alternative medicine as a remedy against rheumatism, inflammation, diabetes and hypertension. Aim: The aim of the study was to evaluate the possible antihypertensive and vasodilator activity of the aqueous extract of Matricaria pubescens (M. pubescens). Material and Methods: In the current study, the aqueous extract of the aerial parts of M. pubescens (AEMP) was prepared and its antihypertensive activity was examined in N(ω)-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Results: The results indicated that AEMP reduced the systolic, diastolic, mean arterial blood pressure in hypertensive rats but not in normotensive rats. The data revealed that AEMP exhibits its antihypertensive effect through vasorelaxant activity. More interestingly, this study approved that the vasorelaxant capacity of AEMP seems to be mediated through vascular cyclooxygenase pathway, the opening of K+ channels and sGC-cGMP induction pathway. Conclusion: The study illustrates the beneficial action of M. pubescens as an antihypertensive agent.

The vasodilatory mechanism of nitric oxide and hydrogen sulfide in human mesenteric artery of colorectal cancer patients: role of potassium channels

Recent studies focused on the role of gasotransmitters in cancer progression and prevention. Therefore, this study was designed to explore the vasodilator activity of NO and H2S in human mesenteric artery of CRC patients via activation of K+ channels. For this purpose, two sets of experiments were established. The blood samples from CRC patients were obtained to detect serum levels of Endocan and MDA. Moreover, the role of K+ channels were assessed in mediating vasodilation of human mesenteric artery in response to SNP and Na2S. The level of serum Endocan was decreased in CRC patients compared to healthy individuals, while serum MDA was not changed. The arterial rings precontracted with NE were first relaxed by cumulative addition of increasing concentrations of either SNP (30nM-30μM) or Na2S (1-6mM). Then maximal relaxation rates were calculated for four times at each 15min intervals. Preincubation of arterial rings for 20min with individual K+ channels blockers were significantly reduced relaxation caused by SNP and Na2S at different time intervals. Furthermore, pretreatment of L-NAME did not change the vasodilation induced by Na2S. Vasodilation of CRC mesenteric unchanged by synergistic application of SNP and Na2S. While preincubation of arterial rings with PAG significantly enhanced vasodilation induced by SNP. In conclusion, these results indicate that endothelial dysfunction and oxidative stress do not take part in the pathogenesis of CRC. The dilatory mechanisms of NO and H2S in mesenteric arteries of CRC patients are K+ channels and time dependent, and the activity of CSE enzyme slows down the vasodilator ability of exogenous NO.

Synthesis and vasodilator activity of 3,4-dihydropyrimidin-2(1H)-ones bearing urea, thiourea, and sulfonylurea moieties

A series of novel 3,4-dihydropyrimidin-2(1H)-ones bearing urea, thiourea, and sulfonylurea moieties were synthesized and pharmacologically evaluated as vasodilator agents. The most interesting vasodilators were the thiourea derivatives 6a and 6b and the urea derivatives 6f–6i and 7f–7h, although the ureas were relatively more active than thioureas. Twenty-fold more active than diazoxide, the urea 6g was the most potent vasodilator (EC50 = 0.983 ± 0.061 μmol/L) and proved to act as a voltage-gated calcium channel blocker. The lack of activity of sulfonylureas, 6k and 7j, could be attributed to their partial ionization at the physiological pH because of their acidic character. It should be interesting to investigate a larger number of compounds, including N-methylated sulfonylureas, to increase the vasodilator activity and to explore other biological models.